Atorvastatin: In animal models, atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; atorvastatin also reduces LDL production and the number of LDL particles.

Ezetimibe: Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. In a 2-week clinical study in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production. Ezetimibe does not inhibit cholesterol synthesis in the liver or increase bile acid excretion. Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of statins.

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate.

Primary Hyperlipidemia: This tablet is indicated for the reduction of elevated total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia.

Homozygous Familial Hypercholesterolemia (HoFH): This tablet is indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

The dosage range is 10/10 mg/day through 80/10 mg/day. Recommended starting dose is 10/10 mg/day or 20/10 mg/day. Recommended starting dose is 40/10 mg/day for patients requiring a greater than 55% reduction in LDL-C. Dosing of this tablet should occur either greater than or equal to 2 hours before or greater than or equal to 4 hours after administration of a bile acid sequestrant.

• Active liver disease or unexplained persistent elevations of hepatic transaminase levels.
• Hypersensitivity to any component of this tablet.
• Women who are pregnant or may become pregnant.
• Nursing mothers.

Patients should be advised to report promptly any unexplained and/or persistent muscle pain, tenderness, or weakness. This tablet should be discontinued immediately if myopathy is diagnosed or suspected.

Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain CYP3A4 inhibitors, fibric acid derivatives, and cyclosporine. Predisposing factors include advanced age (>65), uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported.

Liver enzyme abnormalities: Persistent elevations in hepatic transaminase can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter.

Pregnancy & Lactation

Pregnancy Category X. This tablet is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy. Lipid-lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. It is not known whether atorvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk.